Betaferon

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Interferon beta-1b 0.25 mg (20% excess in quantity filled)
Available from:
Bayer New Zealand Limited
INN (International Name):
Interferon beta-1b 0.25 mg (20% excess in quantity filled)
Dosage:
8 MIU
Pharmaceutical form:
Injection with diluent
Composition:
Active: Interferon beta-1b 0.25 mg (20% excess in quantity filled) Excipient: Albumin Hydrochloric acid Mannitol Sodium hydroxide Hydrochloric acid Sodium chloride Water for injection
Units in package:
Combination pack, 1 (pwdr+diluent syringe+adapter+needle+wipes), 1 dose unit
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Boehringer Ingelheim RCV GmbH & Co KG
Therapeutic indications:
BETAFERON is indicated for: · the treatment of patients with a single clinical event suggestive of multiple sclerosis and at least two clinically silent magnetic resonance imaging (MRI) lesions characteristic of multiple sclerosis, if alternative diagnoses have been excluded, · the treatment of ambulatory patients, with relapsing-remitting multiple sclerosis characterised by at least two attacks of neurological dysfunction over a two year period followed by complete or incomplete recovery. · the reduction of frequency and severity of clinical relapses and for slowing the progression of disease in patients with secondary progressive multiple sclerosis
Product summary:
Package - Contents - Shelf Life: Combination pack, 1 (pwdr+diluent syringe+adapter+needle+wipes) - 1 dose units - 24 months from date of manufacture stored at or below 25°C 3 hours reconstituted stored at 2° to 8°C (Refrigerate, do not freeze) - Combination pack, 15 (pwdr+diluent vial/syringe) - 15 dose units - 24 months from date of manufacture stored at or below 25°C 3 hours reconstituted stored at 2° to 8°C (Refrigerate, do not freeze) - Syringe, diluent - 1.2 mL - 36 months from date of manufacture stored at or below 25°C - Vial, powder - 0.3 mg - 24 months from date of manufacture stored at or below 25°C 3 hours reconstituted stored at or below 25°C - Vial, diluent - 1.2 mL - 36 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-5669
Authorization date:
1995-01-30

1909 BETAFERON

Single Use Pack CMI

BETAFERON

(Bee·ta·feer·on)

interferon beta-1b (rbe)

Consumer Medicine Information

Contents:

What is in this leaflet ……….

What Betaferon is used for ….

Before you use Betaferon …...

How Betaferon is

given/used …………………..

While you are using

Betaferon …………………...

Side effects …………………

After Using Betaferon ………

Product Description …………

Further information …………

WHAT IS IN THIS

LEAFLET

This leaflet answers some common

questions about Betaferon.

It does not contain all the available

information.

It does not take the place of talking

to your doctor or pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you using Betaferon

against the benefits it will have for

you.

If you have any concerns about

taking this medicine, ask your

doctor, nurse or pharmacist.

Keep this leaflet with your

medicine. You may need to read it

again.

WHAT BETAFERON IS

USED FOR

Betaferon belongs to a class of

medicines known as interferons.

Interferons are naturally occurring

proteins, produced by the body that

help fight against attacks on the

immune system such as viral

infections.

The active substance of Betaferon is

interferon beta-1b, a recombinant

human interferon beta produced

from a strain of Escherichia coli.

How it works

Multiple sclerosis (MS) is a long

term condition that affects the

central nervous system (CNS) i.e.

brain and spinal cord. The exact

cause of MS is unknown. An

abnormal response by the body’s

immune system is thought to play an

important part in the process which

damages the CNS.

Betaferon has been shown to change

the response of the immune system

and to help reduce disease activity.

Single clinical event indicating high

risk of developing MS: Betaferon is

for use in patients who for the first

time have experienced symptoms

which indicate a high risk for

development of multiple sclerosis.

Your doctor will rule out any other

reasons which could explain these

symptoms before you are treated.

Relapsing-remitting MS: Betaferon

is for use in patients who have

occasional attacks or relapses during

which symptoms become noticeably

worse (at least two relapses within

the last two years). This is the form

of multiple sclerosis where patients

experience attacks of CNS problems

(for example of visual disturbances,

arm/leg weakness, loss of

bowel/bladder control) separated by

periods of complete or incomplete

recovery.

Betaferon has been shown to cut

down the number of attacks and

make them less severe. It reduces

the number of hospital stays due to

the disease and prolongs the time

without relapses.

Secondary progressive MS:

Betaferon is also for use in patients

whose symptoms progress to

another form of MS called

secondary progressive MS. With

this, patients become increasingly

impaired, whether or not they have

relapses. Betaferon can reduce the

number and severity of the attacks,

and slow the progression of

disability.

Betaferon has been shown to have a

marked effect on those physical

changes in the brain that can be

detected by a special kind of brain

scan.

This medicine is available only

with a doctor's prescription.

Ask your doctor if you have any

questions about why this medicine

has been prescribed for you.

Your doctor may have prescribed it

for another reason.

1909 BETAFERON

Single Use Pack CMI

BEFORE YOU USE

BETAFERON

When you must not use it

Do not use Betaferon if you have

an allergy to:

any medicine containing interferon

beta-1b (rbe), mannitol or human

albumin

any of the ingredients listed at the

end of this leaflet.

Some of the symptoms of an allergic

reaction may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue or

other parts of the body

rash, itching or hives on the skin

Do not use this medicine if you

have liver failure.

Do not use this medicine if you

suffer from epilepsy (fits or

seizures) which is not controlled

by other medicines.

Do not use this medicine after the

expiry date printed on the pack

and blister.

The expiry date is printed on the

carton and on each blister after

“EXP” (e.g. 11 2018 refers to

November 2018). The expiry date

refers to the last day of that month.

If it has expired return it to your

pharmacist for disposal.

Do not use this medicine if the

packaging is torn or shows signs

of tampering.

If the packaging is damaged, return

it to your pharmacist for disposal.

If you are not sure whether you

should start using this medicine,

talk to your doctor.

Before you start to use it

Tell your doctor if you have

allergies to any other medicines,

foods, preservatives or dyes.

Tell your doctor if you have or

have had any of the following

medical conditions:

seizures (fits or convulsions)

severe depression (feeling of

severe sadness and unworthiness)

or thoughts of suicide

heart disorders

kidney disease

liver disease

blood disorder (e.g. low counts of

platelets, red and white blood

cells)

thyroid disease

pancreatitis

an increase of certain type of

blood fats (triglycerides)

allergy to any other medicines,

foods, dyes or preservatives

bone marrow disorder

monoclonal gammopathy

(disorder of immune system

where abnormal proteins are

found in the blood).

Tell your doctor if you are

pregnant or plan to become

pregnant or are breastfeeding.

It is not known whether Betaferon

can affect your developing baby if

you take it during pregnancy.

Women of childbearing age should

take appropriate contraceptive

measures while using Betaferon.

If you become pregnant while

using Betaferon, consider stopping

your treatment and contact your

doctor immediately.

Your doctor can discuss with you

the risks and benefits involved.

It is not known whether Betaferon

passes into breast milk. If you want

to breastfeed while using Betaferon,

discuss this with your doctor. Your

doctor can discuss with you the risks

and benefits involved.

If you have not told your doctor

about any of the above, tell

him/her before you start taking

Betaferon.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including any that you

get without a prescription from

your pharmacy, supermarket or

health food shop.

Care must be taken when Betaferon

is used with some medicines,

including some used to treat fever

and pain.

The following medicines commonly

used by people with MS have been

well tolerated whilst using

Betaferon:

corticosteroids such as

hydrocortisone, prednisone or

prednisolone

ACTH (adrenocorticotrophic

hormone)

Some medicines that are broken

down by the liver and Betaferon

may interfere with each other. These

include:

medicine to treat epilepsy

medicine used for sedation or to

treat anxiety

medicine to treat depression

Your doctor may have to adjust the

dose of your other medicines while

you are using Betaferon. It is

therefore important that you tell

your doctor about all the medicines

that you are taking.

Your doctor and pharmacist have

more information on medicines to be

careful with or avoid while taking

this medicine.

What else you should know

This product contains human

albumin and hence carries an

extremely remote risk for

transmission of viral diseases. A

theoretical risk for transmission

of Creutzfeldt-Jacob Disease

(CJD) is also considered

extremely remote.

It is not known if Betaferon can

decrease your ability to have

children in the future.

During treatment with Betaferon,

your body may produce

substances called neutralising

antibodies, which may react with

Betaferon. It is not yet clear if

these reduce the effectiveness of

the treatment. Neutralising

1909 BETAFERON

Single Use Pack CMI

antibodies are not produced in all

patients.

Betaferon is not recommended for

use in children under 18 years of age

with MS as there is no clinical

experience in this age group.

HOW BETAFERON IS

USED

If you do not understand the

instructions provided, ask your

doctor, MS education nurse or

pharmacist for help.

Follow all directions given to you

carefully.

They may differ from the

information contained in this leaflet.

Betaferon is given as a subcutaneous

(under the skin) injection after

reconstitution every other day.

Treatment with Betaferon should be

started under the supervision of a

specialist doctor experienced in the

treatment of MS.

It is recommended that new users of

Betaferon contact the MS

immunotherapy nurse to assist with

training. A list of contact numbers is

included under Further Information.

The service is available at no cost.

Before administration, the Betaferon

solution for injection has to be

prepared from a vial of Betaferon

and the 1.2 mL of diluent from the

pre-filled syringe.

Each mL of reconstituted solution

for injection contains 8 million IU

(international units) or 0.25 mg

interferon beta-1b (rbe).

The usual dose is 1 mL of the

prepared Betaferon solution for

injection is injected subcutaneously

(under the skin) every other day.

Betaferon should not be injected

directly into the veins.

The instructions included in this

leaflet are for manual self injection.

Auto-injectors are also available for

use with Betaferon. If an auto-

injector is used, please follow

instructions enclosed with your

auto-injector.

How much is given

In general, treatment should be

started at a low dose of 0.25 mL

(0.0625 mg). The dose will then be

increased gradually to the full dose

of 1.0 mL (0.25 mg) which is

equivalent to 8 million IU.

The dose should be increased at

every fourth injection in four steps

(0.25 mL, 0.5 mL, 0.75 mL, 1.0

mL). Your doctor may decide

together with you to change the time

interval for the dose increase

depending on side effects you may

experience at the start of treatment.

Administration will either be done

by your doctor or his/her assistant or

by yourself after you have been

carefully and sufficiently instructed

and trained. To assist you in

subcutaneous self-administration of

Betaferon, detailed instructions for

self-injection are set out below.

These instructions also tell you how

to prepare the Betaferon solution for

injection.

To reduce the risk of the injection

solution becoming contaminated it

should be used as soon as possible

after it is prepared. If required, the

reconstituted solution for injection

may be stored in the refrigerator (not

freezer) at 2

C to 8

C and used

within 3 hours of preparation.

How to inject

Betaferon is intended to be injected

by yourself by subcutaneous (under

the skin) injection. The following

instructions and pictures explain

how to prepare Betaferon for

injection and how to inject

Betaferon yourself.

Please read the instructions

carefully and follow them step by

step. Your doctor or their assistant

will help you to learn the process of

self-administration. Do not attempt

to inject yourself until you are sure

that you understand how to prepare

the injection solution and give the

injection to yourself.

The instructions include the

following main steps:

A. General advice

B. Getting ready to inject

C. Reconstituting the solution, step

by step

D. Drawing up the injection

E. Giving the injection

F. Quick review of the process

A.

General advice

Be consistent, use Betaferon as

described under “How

Betaferon is used” within this

leaflet.

Keep your syringes and syringe

disposal unit out of reach of

children; lock the supplies away

if possible.

Never re-use syringes or

needles.

Always use a sterile (aseptic)

technique as described here. If

in any doubt, discard needles,

syringes or solution and start

again.

Always place the used syringes

in the proper disposal unit.

B.

Getting ready to inject

Choosing an injection site

Before preparing your injection,

decide where you are going to

inject. You should inject Betaferon

into the fatty layer between the skin

and muscle (that is,

subcutaneously, about 8 to 12 mm

under the skin). The best places for

injections are where the skin is

loose and soft, and away from

joints, nerves, or bones, for

example the abdomen, arm, thigh,

or buttocks. Try to avoid the panty

or belt line at the waist and the seat

portion of the buttocks as daily

activity may irritate these areas.

1909 BETAFERON

Single Use Pack CMI

Important: Do not use any area

where you can feel lumps, bumps,

firm knots, pain or an area that is

discoloured, indented, scabbed, or

where skin is broken. Talk to your

doctor or healthcare professional

about these or any other unusual

conditions you may find.

You should rotate the injection site

at every injection. If some areas

are too difficult for you to reach,

you may need to ask your support

person (or someone who has been

trained to give injections) to help

you with these injections. Follow

the sequence described in the

schedule at the end of this leaflet

(see “Rotating injection sites”) and

you will come back to your first

injection site area after 8 injections

(16 days). This will give each

injection site a chance to fully

recover before receiving another

injection.

Please refer to the rotation schedule

at the end of this leaflet to learn

how to choose an injection site. An

example of a medication record is

also included. This should give

you an idea of how you can keep

track of your injection sites and

dates.

Checking the content of the pack

You will find in the Betaferon pack:

1 Betaferon vial (with powder for

solution for injection)

1 pre-filled syringe of diluent for

Betaferon (sodium chloride

solution 5.4 mg/mL (0.54%)).

(Be sure that the tip cap is firmly

attached to the solvent syringe!)

1 vial adapter with a pre-attached

needle

2 alcohol swabs for skin and vial

cleaning.

In addition you will need a disposal

unit for used syringes and needles.

For skin disinfection use an

appropriate disinfectant.

C.

Reconstituting the solution,

step by step

1 – Wash your hands thoroughly with

soap and water before beginning this

process.

2 – Open the Betaferon vial and put it

on the table. It is best to use your

thumb rather than your nail as it

could break.

3 – Clean the top of the vial with an

alcohol wipe, moving the wipe in one

direction only. Leave the wipe on top

of the vial.

4 – Open the blister pack containing

the vial adapter, but leave the vial

adapter inside.

Do not remove the vial adapter

from the blister pack at this stage.

Do not touch the vial adapter. This

is to keep it sterile.

5 – Rest the vial on a flat surface

while attaching the adapter.

6 – Remove the alcohol wipe from

the top of the Betaferon vial. Place

the blister pack containing the vial

adapter on top of the vial. Push it

down with your thumb and forefinger

or the palm of your hand until you

feel it snap into place.

7 – Remove the blister pack from the

vial adapter, holding the blister

edges. Now you are ready to attach

the pre-filled diluent syringe to the

vial adapter.

8 – Pick up the syringe. Remove the

orange tip cap, using a ‘twist-and-

pull’ motion. Throw away the tip

cap.

9 – Connect the syringe to the

opening on the side of the vial

adapter by inserting the end of the

syringe and tightening carefully with

a clockwise “push-and-twist” motion

(see arrow). This will form the

syringe assembly.

10 – Hold the syringe assembly at the

bottom of the vial. Slowly push the

plunger of the syringe in all the way

to transfer all of the diluent into the

vial. Release the plunger.

1909 BETAFERON

Single Use Pack CMI

The plunger may go back to its

original position.

11 – With the syringe assembly still

attached, swirl the vial around gently

to completely dissolve the dry

Betaferon powder.

Do not shake the vial.

12 – Examine the solution carefully.

It should be clear and contain no

particles. If the solution is

discoloured or contains particles,

discard it and start again with a new

single pack of supplies. If foam is

present – which can happen if the vial

is shaken or swirled too much – let

the vial sit undisturbed until the foam

settles.

13 – If the plunger has moved back to

its original position push it in again

and hold it in place. To prepare your

injection, turn the assembly over so

that the vial is on top, cap side

pointing down. Doing this allows the

solution to flow down into the

syringe.

D.

Drawing up the injection

Keep the syringe horizontal.

Slowly pull the plunger back to

withdraw all the solution out of the

vial and into the syringe.

14 – Turn the syringe assembly so

that the needle is pointing up. This

allows any air bubbles to rise to the

top of the solution.

15 – Remove any air bubbles by

gently tapping the syringe and

pushing the plunger to the 1ml mark,

or to the volume prescribed by your

doctor.

If too much solution goes into the

vial along with the air bubbles, pull

the plunger back a little to withdraw

the solution back from the vial into

the syringe. Do this until all the air is

gone and there is 1 ml of

reconstituted solution in the syringe.

Important: You will need to hold the

syringe assembly to a horizontal

position with the vial on top when

withdrawing solution again.

16 – Next, hold the blue vial adapter

with the attached vial and remove it

from the syringe by twisting it and

then pulling it down, away from the

syringe.

Only hold the blue plastic adapter

when removing. Keep the syringe

in a horizontal position and the vial

below the syringe.

17 – Removing the vial and adapter

from the syringe (using the twist and

pull motion) ensures that the

solution will flow out from the

needle when injected.

18 – Dispose of the vial and any

unused portion of the solution in the

disposal unit.

You are now ready to inject.

If, for some reason, you are not able

to inject the Betaferon immediately,

you can keep the reconstituted

solution in the syringe in a

refrigerator for up to 3 hours before

using. Do not freeze the solution,

and do not wait longer than 3 hours to

inject it. If more than 3 hours pass,

discard the reconstituted Betaferon

solution and prepare a new injection.

When you use the solution, warm it

up in your hands before injecting to

avoid pain.

E.

Giving the injection

subcutaneously (under the

skin)

1 – Choose an area for the injection

(see advice at the start and diagrams

at the end of this leaflet), and make a

note of it in your medication record.

2 – Use an alcohol swab to clean the

skin at the injection site. Let the skin

air-dry. Throw the swab away.

For skin disinfection use an

appropriate disinfectant.

1909 BETAFERON

Single Use Pack CMI

3 – Remove the cap from the needle.

Pull the cap, do not twist it.

4 – Gently pinch the skin together

around the disinfected injection site

(to raise it up a little).

Please follow manufacturer’s

instructions for use with an auto-

injector. Alternatively, for manual

injection:

5 – Holding the syringe like a pencil

or a dart, push the needle straight into

the skin at a 90º angle with a quick,

firm motion.

6 – Inject the medicine using a slow,

steady push on the plunger. (Push the

plunger all the way in until the

syringe is empty.)

7 – Discard the syringe in the

disposal unit.

F.

Quick review of the process

Take out the contents of the

pack

Attach vial adapter to the vial

Connect the syringe to the vial

adapter

Push syringe plunger to transfer

diluent into the vial

Turn the syringe assembly

over, then pull out the plunger

Remove vial from syringe ––

you are now ready to inject

NOTE: The injection should be

administered immediately after

mixing (if the injection is delayed,

refrigerate the solution and inject it

within 3 hours). Do not freeze.

Rotating injection sites

You need to choose a new site for

each injection to allow the area

time to recover and help prevent

infection. Advice on which areas

to choose is given in the first part

of this leaflet. It is a good idea to

know where you plan to inject

before you prepare your syringe.

The schedule shown in the diagram

below will help you to vary the

sites appropriately. For example,

give the first injection into the right

side of the abdomen, choose the left

side for the second injection, then

move to the right thigh for the

third, and so on through the

diagram until all suitable areas of

the body have been used. Keep a

record of where and when you last

gave yourself an injection. One

way to do that is to note the

injection site on the enclosed

medication record card.

By following this schedule, you

will come back to your first area

(e.g. the right side of the abdomen)

after 8 injections (16 days). This is

called a Rotation Cycle. On our

example schedule each area is split

again into 6 injection sites (which

adds up to 48 injection sites all

together), left, right, upper, middle

and lower part of each area. If you

come back to an area after one

Rotation Cycle, choose the most

distant injection site within this

area. If an area becomes sore, talk

to your doctor or nurse about

choosing other injection sites.

Rotation Schedule:

To help you rotate the injection

sites appropriately we recommend

that you keep a record of the date

and location of your injection. You

can use the following rotation

schedule.

Work through each rotation cycle

in turn. Each cycle will be 8

injections (16 days), given in an

area 1 through to area 8 in turn. By

following this sequence, you will

give each area a chance to recover

before receiving another injection.

Rotation Cycle 1:

Upper left

section of

each area.

Rotation Cycle 2:

Lower right

section of

each area.

Rotation Cycle 3:

Middle left

section of

each area.

Rotation Cycle 4:

Upper right

section of

each area

BETAFERON Medication

record

Instructions for keeping track

of your injection sites and

dates

Start with your first injection

(or your last injection if you

are not a new Betaferon

user).

Select an injection site. If

you have already been using

Betaferon, start with the area

that has not been used during

the last rotation cycle, i.e. the

past 16 weeks.)

After your injection, fill in

the used injection site and

date on the table in your

injection record (see the

example: Keeping track of

your injection sites and

dates).

How long to take it

The length of treatment will be

decided by you and your doctor.

If you forget to use it

If you have forgotten to give

yourself an injection at the right

time, do it as soon as you remember

and then follow on with the next one

48 hours later. Do not take a double

dose to make up for the forgotten

single dose.

Ask your doctor if you are not sure

what to do or have trouble

remembering to inject your

medicine.

1909 BETAFERON

Single Use Pack CMI

If you stop using Betaferon

Talk to your doctor if you stop or

wish to stop treatment. Stopping

Betaferon is not known to lead to

acute withdrawal symptoms.

If you inject too much

(overdose)

Administration of many times the

dose of Betaferon recommended for

treatment of multiple sclerosis has

not led to life-threatening situations.

In case of accidental overdose (e.g.

one injection every 24 hours instead

of every 48 hours), contact your

doctor or the Poisons Information

Centre (In Australia telephone 131

126, in New Zealand telephone 0800

764 766) for recommendations on

the management and treatment of

overdosage.

WHILE YOU ARE USING

BETAFERON

Things you must do

If you are about to be started on

any new medicine, remind your

doctor and pharmacist that you

are taking Betaferon.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are taking this medicine.

If you become pregnant while

taking this medicine, tell your

doctor immediately.

Keep all of your doctor’s

appointments so that your

progress can be checked.

Your doctor may also take blood

tests prior to commencing and

regularly during treatment with

Betaferon to test for changes in your

blood count, liver function and

thyroid function.

Tell your doctor immediately if you:

experience depression or suicide

thoughts

experience symptoms such as

itching, swelling of face and/or

your tongue or sudden shortness

of breath. These may be

symptoms of a serious allergic

reaction (hypersensitivity) that

may become life threatening.

experience irregularity of your

heart beats or fluid retention

(swelling) in the lower parts of

your body (e.g. ankles, legs) or

shortness of breath. These may

be symptoms of a disease of the

heart muscle which has been

reported in rare cases during

treatment with Betaferon

Tell your doctor if you:

suffer from signs of frequent

infections such as fever or sore

throat; notice unusual bruising or

excessive bleeding after injury.

notice a yellowish colouration of

your skin or eyes (jaundice), loss

of appetite, or fatigue.

Injection site skin breakdown and

tissue destruction can be extensive

and may involve scar formation. If

you have multiple lesions, Betaferon

must be discontinued until healing

has taken place. Patients with single

lesions may continue on Betaferon

provided the necrosis is not too

extensive, as some patients have

experienced healing of injection site

necrosis while on Betaferon.

To minimise the risk of injection site

necrosis you must:

use an aseptic technique

rotate the injection sites with

each dose

The procedure of self-administration

must be reviewed periodically by your

doctor, especially if injection site

reactions have occurred.

Things you must not do

Do not use Betaferon to treat any

other complaints.

Do not stop using Betaferon, or

change the dose, without first

checking with your doctor.

Do not give this medicine to

anyone else, even if their

symptoms seem similar to yours

or if they have the same condition

as you.

Things to be careful of

The effects of the disease or of

Betaferon treatment may influence

your ability to drive a car or operate

machinery. You should discuss this

with your doctor if you are

concerned.

SIDE EFFECTS

Tell your doctor as soon as

possible if you do not feel well

while you are taking Betaferon.

Betaferon helps most people with

MS, but it may have unwanted side

effects in a few people. All

medicines can have side effects.

Sometimes they are serious, most of

the time they are not. You may need

medical treatment if you get some of

the side effects.

1909 BETAFERON

Single Use Pack CMI

Do not be alarmed by this list of

possible side effects. You may not

experience any of them.

At the beginning of treatment, side

effects are common but in general

they become less with further

treatment.

Ask your doctor or pharmacist to

answer any questions you may

have.

Tell your doctor if you notice any

of the following and they worry

you.

This list contains the more

common side effects of your

medicine:

Injection site reactions

including redness, swelling

bruising, pain or itching. These

may be reduced by

administration with an

autoinjector. Please consult

your doctor for further

information.

Flu-like symptoms including

fever, chills, muscular pain,

headache, tiredness, painful

joints, general feeling of being

unwell, or sweating. These may

be relieved if paracetamol or

ibuprofen is taken when the

injection is given.

This list contains the other

common side effects of your

medicine:

Redness, swelling,

discolouration, pain, allergy,

skin cell-death where the

injection was given. These

tend to be worst at the start of

treatment and become less of a

problem over time. If you

experience multiple skin sores,

very severe sores or breakage

of the skin associated with

swelling or drainage of fluid

from the injection site you

should discuss this with your

doctor. It may be necessary to

stop using Betaferon until these

are healed.

Rash, itchiness, urticaria

(hives), skin discolouration,

sweating.

Nausea, vomiting, diarrhoea,

constipation, abdominal pain

Dizziness, anxiety, nervousness

Infected sinus

Conjunctivitis.

If any of the side effects get serious,

tell your doctor or pharmacist.

The list below includes the less

common side effects of your

medicine:

Migraine

Palpitations

High blood pressure

Menstrual period upsets

Depression, emotional

instability, convulsions (fits),

suicide attempts, and confusion

Blood disorders

Muscle pain and stiffness

Muscle weakness

Shortness of breath, wheeze

Chest pain

Pelvic pain

Abnormal vision

Back pain

Fast heart beat

Kidney problems

The following list includes the

very rare side effects of your

medicine:

Disease of the heart muscle

When Betaferon has been given

to patients who have a very rare

disease where abnormal

proteins are found in the blood

there have been problems with

small blood vessels leading to

collapse and even death

Loss of scalp hair

Serious allergic reactions

Disturbances of the thyroid

gland

Hepatitis, liver failure

Cystitis

Breast pain

Joint pain

Menorrhagia (heavy

menstruation)

Infection

Insomnia

Urinary disorders

Anorexia

Convulsion

Changes in weight

If any of the following happen, tell

your doctor immediately or go to

Accident and Emergency at your

nearest hospital:

sudden signs of allergy such as

rash, itching or hives on the skin,

swelling of the face, lips, tongue

or other parts of the body

shortness of breath, wheezing or

trouble breathing

yellowing of the skin and/or eyes

(jaundice)

These are rare but very serious side

effects. You may need urgent

medical attention or hospitalisation.

Tell your doctor or pharmacist if

you notice anything that is making

you feel unwell.

Other side effects not listed above

may also occur in some people.

AFTER USING

BETAFERON

Storage

Keep Betaferon in the original

pack until it is time for it to be

used/given.

Keep Betaferon in a cool dry place

where the temperature stays

below 25°C before reconstitution.

Do not freeze.

Keep it where children cannot

reach it. A locked cupboard at least

one-and-a half metres above the

ground is a good place to store

medicines.

After preparing the solution, you

should use it immediately. However,

if you are not able to do so, you can

store the reconstituted solution in the

refrigerator between 2 to 8°C for up

to 3 hours. (Refrigerate. Do Not

Freeze).

When you use the solution, warm it

up in your hands before injecting to

avoid pain. Do not use Betaferon if

1909 BETAFERON

Single Use Pack CMI

you notice it contains particles or if

it is discoloured.

Once you have administered the

injection, you should throw any

unused portion away.

Disposal

Betaferon should be used once only.

After injecting, you should discard

the syringe even if you have not

injected all its contents. Syringes

should be discarded in an

appropriate disposal unit.

If your doctor tells you to stop using

Betaferon or if it has passed its

expiry date, ask your doctor or

pharmacist what to do with any

syringes that are left over.

PRODUCT

DESCRIPTION

What it looks like

Betaferon is a sterile white to off-

white powder for solution for

injection.

Betaferon is available in a carton

containing 15 single use packs.

Each single use pack contains

- 1 Betaferon vial with powder for

injection

- 1 pre-filled syringe containing

diluent

- 1 vial adapter with needle and

- 2 alcohol swabs.

Ingredients

Active ingredients:

Betaferon – 0.25 mg interferon

beta-1b (rbe) per mL

Inactive ingredients:

mannitol

human albumin

0.54 % sodium chloride

solution (as diluent).

The inactive ingredients of

Betaferon include small amounts of

mannitol (a naturally occurring

sugar) and human albumin (a

protein). If you know that you are

hypersensitive to any of the

ingredients or if you become so, you

must not use Betaferon.

Further information

You can obtain more information

from your doctor, pharmacist or the

MS Society in your State.

https://www.nps.org.au/australian-

prescriber/articles/ms-australia

NSW free call: 1800 042 138

TAS free call: 1800 676 721

Patient support kits that include a

step-by-step instruction DVD and

video are available.

Supplier

Made in Germany for:

Bayer Australia Limited

ABN 22 000 138 714

875 Pacific Highway

Pymble, NSW 2073

Bayer New Zealand Limited

3 Argus Place, Hillcrest

North Shore, Auckland 0627

Freephone 0800 229 376

Australian Registration

number

Betaferon - AUST R 83309

Date of preparation

September 2019

See TGA website

(www.ebs.tga.gov.au) for latest

Australian Consumer Medicine

Information.

See MEDSAFE website

(www.medsafe.govt.nz) for latest

New Zealand Consumer Medicine

Information.

Registered Trademark of the

Bayer Group, Germany

© Bayer Australia Ltd

All rights reserved

1902 BETAFERON DS

Page 1 of 23

NEW ZEALAND DATA SHEET

PRODUCT NAME

BETAFERON® Interferon beta-1b 8 MIU Injection with diluent

QUALITATIVE AND QUANTITATIVE COMPOSITION

Lyophilisate and solvent for solution for injection.

BETAFERON® Recombinant Interferon beta-1b 0.25 mg (8.0 million IU) per mL when reconstituted.

1 mL of the reconstituted solution for injection contains 8 million IU (0.25 mg) of interferon beta-1b.

1 mL solution for injection contains 5.4 mg sodium chloride.

Interferon beta-1b is produced in Escherichia coli cells by recombinant DNA technology (from a strain

of Escherichia coli that bears a genetically engineered plasmid containing a modified human interferon

beta gene).

For the full list of Excipients, see section 6.1 List of excipients.

PHARMACEUTICAL FORM

BETAFERON is presented as a sterile lyophilised white to off-white cake or powder and solvent for

solution for injection.

CLINICAL PARTICULARS

Therapeutic indications

BETAFERON is indicated for:

the treatment of patients with a single clinical event suggestive of multiple sclerosis and at

least two clinically silent magnetic resonance imaging (MRI) lesions characteristic of multiple

sclerosis, if alternative diagnoses have been excluded,

the treatment of ambulatory patients, with relapsing-remitting multiple sclerosis

characterised by at least two attacks of neurological dysfunction over a two year period

followed by complete or incomplete recovery.

the reduction of frequency and severity of clinical relapses and for slowing the progression

of disease in patients with secondary progressive multiple sclerosis

Dose and method of administration

Treatment with BETAFERON should be initiated under the supervision of a physician experienced in

the treatment of multiple sclerosis. There are follow-up data under controlled clinical trial conditions

for patients with relapsing – remitting multiple sclerosis for up to 5 years and for patients with

secondary progressive multiple sclerosis for up to 3 years. Non-controlled follow up data for patients

with secondary progressive MS exist for up to 4.5 years.

The recommended dose of BETAFERON is 0.25 mg (8 million IU), contained in 1 mL of the reconstituted

solution (see Special precautions for disposal and other handling), to be injected subcutaneously every

other day.

1902 BETAFERON DS

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Single Clinical Event Suggestive of Multiple Sclerosis

For a single clinical event suggestive of multiple sclerosis, dose titration is recommended at the start

of treatment.

Patients should be started at 2 million IU (0.0625 mg) contained in 0.25 mL of solution

subcutaneously every other day, and increased slowly to a dose of 8 million IU (0.25mg) contained in

1.0 mL of solution every other day. The titration period may be adjusted according to individual

tolerability.

In the BENEFIT study in patients with a single clinical event, dosage was increased as shown in the

table below.

Table A: Schedule for dose titration*

Treatment Day

Dose

Volume

1, 3, 5

0.0625 mg (2 million IU)

0.25 mL

7, 9, 11

0.125 mg (4 million IU)

0.5 mL

13, 15, 17

0.1875 mg (6 million IU)

0.75 mL

>19

0.25 mg (8 million IU)

1.0 mL

*Titration scheme as used in the BENEFIT study in patients with a single clinical event suggestive of multiple

sclerosis.

In patients with a single clinical event suggestive of multiple sclerosis, efficacy has been

demonstrated over a period of five years.

Relapsing-remitting Multiple Sclerosis

For relapsing-remitting multiple sclerosis the recommended dose of BETAFERON (interferon beta-

1b) is 0.25 mg (8 million IU), contained in 1 mL of the reconstituted solution to be injected

subcutaneously every other day.

Treatment should start as soon as the definite diagnosis of relapsing-remitting multiple sclerosis has

been made and the patient has had at least two exacerbations in the previous two years. In case

there are fewer than two relapses during the last two years the decision should be made on an

individual basis; the treating physician should inform the patient on the possible risk and benefit of a

treatment with interferon beta-1b and decide with him/her whether he/she would be willing to

accept possible side effects and inconveniences that might be related to the treatment with

interferon beta-1b.

For relapsing-remitting MS, the available data for up to 5 years suggest sustained treatment efficacy

of BETAFERON over the whole time period.

Secondary Progressive Multiple Sclerosis

For secondary progressive multiple sclerosis the recommended dose of BETAFERON (interferon

beta-1b) is 0.25 mg (8 million IU), contained in 1 mL of the reconstituted solution to be injected

subcutaneously every other day.

Treatment should start as soon as the definite diagnosis of secondary progressive multiple sclerosis

has been made. For secondary progressive MS, efficacy for a period of two years with limited data

1902 BETAFERON DS

Page 3 of 23

for a period of up to three years of treatment has been demonstrated under controlled clinical trial

conditions.

According to the results of the clinical studies the treatment should last at least two years. The

follow-up studies in relapsing-remitting patients indicate a persistence of the treatment effect until

the end of four to five years. Since the statement on the efficacy after four to five years is based on

a small number of patients, a decision for long-term treatment should be made on an individual

basis by the treating physician.

At the present time it is not known for how long the patient should be treated. Efficacy for a period

of up to three years of treatment has been demonstrated in a controlled clinical trial.

Paediatric population

Efficacy and safety of BETAFERON were not investigated systematically in children and adolescents

under 18 years of age.

Method of administration

For instructions on reconstitution of the medicine before administration, see Section 6.6 Special

precautions for disposal and other handling.

Contraindications

BETAFERON is contraindicated in patients with a history of hypersensitivity to natural or recombinant

interferon beta or human albumin or any of the excipients.

BETAFERON is also contraindicated during pregnancy and in patients with decompensated liver

disease or with epilepsy not adequately controlled by treatment.

Special warnings and precautions for use

Immune System Disorders

The administration of cytokines to patients with pre-existing monoclonal gammopathy has been

associated with the development of systemic capillary leak syndrome with shock-like symptoms and

fatal outcome.

Serious

hypersensitivity

reactions

(rare

severe

acute

reactions

such

bronchospasm,

anaphylaxis, urticaria) may occur. If reactions are severe, BETAFERON should be discontinued and

appropriate medical intervention instituted. Other moderate to severe adverse experiences may

require modifications of the interferon beta-1b dosage regimen or even discontinuation of the agent.

Gastrointestinal Disorders

rare

cases,

pancreatitis

observed

with

BETAFERON

use,

often

associated

with

hypertriglyceridemia.

Depression and Suicide

Patients to be treated with interferon beta-1b should be informed that depression and suicidal

ideation may be a side effect of the treatment and should report these symptoms immediately to the

prescribing physician. In rare cases these symptoms may result in a suicide attempt. Patients

exhibiting depression and suicidal ideation should be monitored closely and cessation of therapy

should be considered.

1902 BETAFERON DS

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In the study with patients with a single demyelinating event suggestive of MS and in the study with

patients with secondary progressive multiple sclerosis, there were no significant differences between

BETAFERON treated patients and placebo treated patients for depression and suicidal ideation.

However, as it cannot be excluded that BETAFERON treatment may be associated with depression and

suicide in individual patients, BETAFERON should be administered with caution to patients with

previous or current depressive disorders or suicidal ideation.

Nervous System Disorders

This product contains human albumin, a derivative of human blood. Based on effective donor

screening and product manufacturing processes, it carries an extremely remote risk for transmission

of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) is also

considered extremely remote. No cases of transmission of viral diseases or CJD have ever been

identified for albumin.

BETAFERON should be administered with caution to patients with a history of seizures.

BETAFERON

should be

withdrawn from patients who develop seizures while on medication until the cause of the

seizure is investigated. If it is determined that BETAFERON is not the cause of the seizure, treatment

can be reinitiated

Laboratory Tests

In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis,

complete blood and differential white blood cell counts, platelet counts, and blood chemistries,

including liver function tests (e.g. AST (SGOT), ALT (SGPT) and

-GT), are recommended prior to

initiation and at regular intervals (one, three and six months) following introduction of BETAFERON

therapy, and then periodically thereafter in the absence of clinical symptoms. Thyroid function tests

are recommended regularly in patients with a history of thyroid dysfunction or as clinically indicated.

Patients with anaemia, thrombocytopenia, leukopaenia (alone or in combination) may require more

intensive monitoring of complete blood cell counts, with differential and platelet counts.

Endocrine Function

Thyroid function tests are recommended regularly in patients with a history of thyroid dysfunction or

as clinically indicated.

Hepatobiliary Disorders

Asymptomatic elevations of serum transaminases, in most cases mild and transient, occurred very

commonly in patients treated with BETAFERON during clinical trials. Rare cases of severe hepatic injury

including cases of hepatic failure and transplant have been reported during post-marketing safety

surveillance.

The most serious events often occurred in patients exposed to other drugs or substances known to be

associated with hepatotoxicity or in the presence of co-morbid medical conditions (e.g. metastasising

malignant disease, severe infection and sepsis and alcohol abuse). Patients should be monitored for

signs of hepatic injury.

occurrence

elevations

serum

transaminases

should

lead

close

monitoring

investigation, including liver function tests (e.g. AST (SGOT), ALT (SGPT) and

-GT), which are

recommended at regular intervals following the introduction of BETAFERON therapy, and then

periodically thereafter in the absence of clinical symptoms.

1902 BETAFERON DS

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Withdrawal of BETAFERON should be considered if the levels significantly increase or if they are

associated with clinical symptoms suggesting the development of hepatitis e.g. jaundice. In the

absence of clinical evidence for liver damage and after normalisation of liver enzymes a reintroduction

of therapy could be considered with appropriate follow-up of hepatic function.

Renal function

In patients with renal impairment, renal function should be monitored carefully when such patients

receive BETAFERON therapy.

Thrombotic microangiopathy

Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura and

haemolytic uraemic syndrome have been reported with interferon beta therapy, including fatal

cases (see Undesirable effects). Cases have been reported several weeks to years after starting

interferon beta products.

Monitoring of early symptoms in all patients is recommended e.g. new onset hypertension, impaired

renal function and thrombocytopenia. Prompt treatment is required and discontinuation of

interferon is recommended.

Nephrotic Syndrome

Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal

segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative

glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during

treatment with interferon-beta therapies (see Undesirable effects). Events were reported at various

time points during treatment and may occur after several years of treatment with interferon-beta.

Periodic monitoring of early signs or symptoms e.g. oedema, proteinuria and impaired renal function

is recommended, especially in patients at higher risk of renal disease. Prompt treatment of nephrotic

syndrome is required and discontinuation of interferon should be considered.

Cardiac Disorders

BETAFERON should be used with caution in patients with pre-existing significant cardiac disease such

as congestive heart failure, coronary artery disease or arrhythmias. While there is no evidence of a

direct cardiotoxic potential for BETAFERON, these patients should be monitored for worsening of

their cardiac condition. This applies particularly during initiation of treatment with BETAFERON,

where flu-like symptoms, commonly associated with beta interferons, exert cardiac stress through

fever, chills and tachycardia. This may aggravate cardiac symptoms in patients with pre-existing

significant cardiac disease. Such patients should be closely observed for worsening of their cardiac

disease during therapy with BETAFERON.

During the post-marketing period very rare reports have been received of worsening of cardiac status

in patients with pre-existing significant cardiac disease, temporally associated with the initiation of

BETAFERON therapy. Rare cases of cardiomyopathy have been reported: if this occurs and a

relationship to BETAFERON is suspected, treatment should be discontinued.

Administration Site Conditions

Injection site necrosis (ISN) has been reported in patients using BETAFERON. It can be extensive and

may involve muscle fascia as well as fat and therefore can result in scar formation. Occasionally

debridement and less often skin grafting, is required and healing may take up to 6 months.

1902 BETAFERON DS

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If the patient experiences any break in the skin, which may be associated with swelling or drainage of

fluid from the injection site, the patient should be advised to consult with their physician before

continuing with injections of BETAFERON.

If the patient has multiple lesions, BETAFERON should be discontinued until healing has occurred.

Patients with single lesions may continue on BETAFERON provided the necrosis is not too extensive,

as some patients have experienced healing of injection site necrosis whilst on BETAFERON.

To minimise the risk of injection site necrosis patients should be advised to:

use an aseptic injection technique

rotate the injection sites with each dose.

The incidence of injection site reactions may be reduced by the use of an auto-injector. In the pivotal

study of patients with a single clinical event suggestive of multiple sclerosis an auto-injector was used

in the majority of patients. Injection site reactions as well as injection site necroses were observed

less frequently in this study than in the other pivotal studies.

The procedure for self-administration by the patient should be reviewed periodically especially if

injection site reactions have occurred.

SPECIFIC PATIENT GROUPS

Paediatric Use

Efficacy and safety of BETAFERON has not been investigated in children and adolescents less than 18

years of age. However, limited data suggest that the safety profile in adolescents from 12 to 16 years

of age receiving 250 microgram BETAFERON subcutaneously every other day is similar to that seen in

adults.

There is only limited information on the use of BETAFERON in children under 12 years of age and,

therefore, BETAFERON should not be administered to this age group.

Interaction with other medicines and other forms of interaction

No formal drug interaction studies have been carried out with BETAFERON. The effect of alternate-

day administration of 0.25 mg (8 million IU) of BETAFERON on drug metabolism in MS patients is

unknown.

Corticosteroid or ACTH treatment of relapses for periods of up to 28 days has been well tolerated in

patients receiving BETAFERON. However, in the clinical trials, patients receiving interferon beta-1b

had a significantly reduced steroid usage compared with placebo patients. Due

to the

lack of clinical

experience in MS patients, the use of interferon beta-1b together with immunomodulators, other

than corticosteroids or ACTH, is not recommended.

Interferons have been reported to cause a down regulation of hepatic cytochrome P450-dependent

enzymes in humans and animals. Caution should be exercised when BETAFERON is administered in

combination with medicinal products that have a narrow therapeutic index and are largely

dependent on the hepatic cytochrome P450 system for clearance, e.g. anti-epileptics. Caution

should be exercised with any co-medication, which has an effect on the hematopoietic system.

1902 BETAFERON DS

Page 7 of 23

Fertility, pregnancy and lactation

Use in Pregnancy

Pregnancy category D. (Medicines which have caused, are suspected to cause or may have expected

to cause, an increased incidence of human foetal malformations or irreversible damage. These

medicines may also have adverse pharmacological effects).

It is not known whether BETAFERON can cause foetal harm when administered to a pregnant woman

or can affect human reproductive capacity. Spontaneous abortions have been reported in subjects

with MS in controlled clinical trials.

Recombinant human interferon beta-1b was not teratogenic in studies with rhesus monkeys at doses

up to 13.3 million IU/kg/day SC but demonstrated an abortifacient activity when administered at doses

ranging from 0.89 to 24 million IU/kg/day. Therefore, BETAFERON is contraindicated during pregnancy

and women of childbearing potential should take appropriate contraceptive measures. If the patient

becomes pregnant or plans to become pregnant while taking BETAFERON, she should be informed of

the potential hazards and it should be recommended to discontinue therapy.

Use in Lactation

It is not known whether interferon beta-1b is excreted in human milk. Because of the potential for

serious adverse reactions to BETAFERON in infants being breast-fed, a decision should be made

whether nursing or the drug should be discontinued.

Effects on ability to drive and use machines

This has not been investigated.

Central nervous system-related adverse events associated with the use of BETAFERON, although

unlikely, may have an influence on the ability to drive and use machines in susceptible patients.

Undesirable effects

Experience with interferon beta-1b in patients with MS is limited, consequently adverse events with

low incidence may not yet have been observed. Table 1 below lists the adverse experiences reported

at an incidence of

2% by 124 relapsing remitting MS patients receiving 8 million IU of BETAFERON

in multicentre clinical trials conducted in the United States and Canada. The adverse events

reported in the secondary progressive study (360 patients) were consistent with the known side

effect profile; the most frequently reported adverse events reported in this study are shown in Table

2 below.

Injection site reactions (e.g. redness, swelling, discolouration, inflammation, pain, hypersensitivity,

necrosis, and non-specific reactions) occurred frequently after administration of BETAFERON. The

incidence rate of injection site reactions usually decreased over time. The use of auto-injectors may

reduce the intensity and frequency of skin reactions.

Inflammation and pain at the injection site is very common. Redness, swelling, discoloration,

hypersensitivity, necrosis and non-specific reactions were significantly associated with 0.25 mg (8

million IU) BETAFERON treatment. The occurrence of necrosis at the injection site is common.

Lymphadenopathy has also been reported. The incidence rate of injection site reactions usually

decreased over time.

1902 BETAFERON DS

Page 8 of 23

Flu-like symptom complex has been seen frequently. This includes fever and chills which are very

common, myalgia which is uncommon, malaise and sweating which occur rarely and headache and

arthralgia. The incidence rate of the symptoms decrease over time. Generally, dose titration is

recommended at the start of treatment in order to increase tolerability to BETAFERON (see Dose

and method of administration). Flu-like symptoms may also be reduced by administration of non

steroidal inflammatory medicines.

Serious hypersensitivity reactions (rare but severe acute reactions such as bronchospasm,

anaphylaxis, urticaria) may occur. If reactions are severe, interferon beta-1b should be discontinued

and appropriate medical intervention instituted.

Table 1: Adverse Reactions and Laboratory Abnormalities Reported in Multicentre Trials (United

States & Canada) in relapsing remitting patients

Adverse Reaction

Placebo

n = 123

Interferon beta-1b

0.25 mg

(8 million IU)

n = 124

Body as a Whole

Injection site reaction*

Headache

Fever*

Flu-like symptom complex*

Pain

Asthaenia*

Chills*

Abdominal pain

Malaise*

Generalized oedema

Pelvic pain

Injection site necrosis*

Cyst

Necrosis

Suicide attempt

Cardiovascular System

Migraine

Palpitation*

Hypertension

Tachycardia

Peripheral vascular disorder

Haemorrhage

Digestive System

Diarrhoea

Constipation

Vomiting

Gastrointestinal disorder

Endocrine System

Goitre

1902 BETAFERON DS

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Adverse Reaction

Placebo

n = 123

Interferon beta-1b

0.25 mg

(8 million IU)

n = 124

Haematological and Lymphatic System

Lymphocytes less than

1500/mm

ANC < 1500/mm

WBC < 3000/mm

Lymphadenopathy

Metabolic and Nutritional Disorders

SGPT > 5 times baseline*

Glucose < 55 mg/dL

Total bilirubin > 2.5 times baseline

Urine protein > 1+

SGOT > 5 times baseline*

Weight gain

Weight loss

4%

Musculoskeletal System

Myalgia*

Myasthaenia

13%

Nervous System

Dizziness

Hypertonia

Anxiety

Nervousness

Somnolence

Confusion

Speech disorder

Convulsion

Hyperkinesia

Amnaesia

0%

2%

Respiratory System

Sinusitis

Dyspnoea*

Laryngitis

6%

Skin and Appendages

Sweating*

Alopecia

4%

Special Senses

Conjunctivitis

Abnormal vision

7%

1902 BETAFERON DS

Page 10 of 23

Adverse Reaction

Placebo

n = 123

Interferon beta-1b

0.25 mg

(8 million IU)

n = 124

Urogenital System

Dysmenorrhoea

Intermenstrual spotting*

Metrorrhagia

Cystitis

Breast pain

Menorrhagia

Urinary urgency

Fibrocystic breast

Breast neoplasm

* Significantly associated with interferon beta-1b treatment.

Table 2: Frequently reported adverse events in the secondary progressive study

Adverse reaction

Placebo

n = 358

Interferon beta-1b

0.25 mg

(8 million IU)

n = 360

Body as a whole*

Asthaenia

Flu syndrome*

Fever*

Pain

Back pain

Chills*

88.5%

56.4%

37.2%

13.1%

20.7%

21.8%

7.3%

96.4%

60.0%

59.2%

39.4%

23.3%

23.3%

21.9%

Injection site*

Injection site inflammation*

Injection site reaction*

19.8%

4.2%

10.3%

77.5%

50.0%

43.6%

Musculoskeletal system

Myasthaenia

Myalgia*

55.3%

37.2%

8.9%

61.9%

36.4%

22.8%

Nervous system

Headache

Neuropathy**

Paresthaesia

Abnormal gait

Muscular hypertonia*

Depression

Ataxia

93.9%

39.7%

39.1%

37.4%

33.2%

27.4%

28.8%

22.1%

93.6%

45.6%

33.3%

32.2%

33.6%

37.8%

24.4%

18.9%

Respiratory system

Rhinitis

53.1%

29.9%

50.8%

25.6%

1902 BETAFERON DS

Page 11 of 23

Skin and appendages

Rash*

34.1%

10.6%

38.9%

21.4%

Urogenital system

Urinary tract infection

55.9%

22.6%

51.1%

18.9%

Significantly associated with interferon beta-1b treatment (p < 0.05)

“Neuropathy” was used in the study as the HARTS term for recording MS symptoms

Subject count for each individual adverse event term. Subjects who had more than one adverse event are thus

counted more than once. The table does not count multiple occurrences of the same event in one patient.

Table 3: Adverse Events and Laboratory Abnormalities reported in the BENEFIT study

#

(single

clinical event suggestive of multiple sclerosis).

Adverse Reaction

Placebo

n = 176

BETAFERON

n = 292

Infections and infestations

Infection

Abscess

Blood and lymphatic system disorders

Lymphocyte count decreased (<1500/mm

Absolute neutrophil count decreased

(<1500/mm

White blood cell count decreased

(<3000/mm

Lymphadenopathy

Metabolism and nutrition disorders

Blood glucose decreased (<55 mg/dL)

Psychiatric disorders

Depression

Anxiety

Nervous system disorders

Headache

Dizziness

Insomnia

Migraine

Paresthesia

Eye disorders

Conjunctivitis

Abnormal vision

Ear and labyrinth disorders

Ear pain

1902 BETAFERON DS

Page 12 of 23

Adverse Reaction

Placebo

n = 176

BETAFERON

n = 292

Cardiac disorders

Palpitation

Vascular disorders

Vasodilatation

Hypertension

Respiratory, thoracic and mediastinal

disorders

Upper respiratory infection

Sinusitis

Cough increased

Dyspnoea

Gastrointestinal disorders

Diarrhoea

Constipation

Nausea

Vomiting

Abdominal pain

Hepatobiliary disorders

Alanine aminotransferase increased (SGPT >5

times baseline)

Aspartate aminotransferase increased (SGOT

>5 times baseline)

Skin and subcutaneous tissue disorders

Skin disorder

Rash

Renal and urinary disorders

Urinary retention

Urinary protein positive (>1+)

Urinary frequency

Urinary incontinence

Urinary urgency

Reproductive system and breast disorders

Dysmenorrhoea

Menstrual disorder

Metrorrhagia

Impotence

General disorders and administration site

conditions

Injection site reaction (various kinds)

^ §

Injection site necrosis

Flu-like symptoms

Fever

Pain

Chest pain

1902 BETAFERON DS

Page 13 of 23

Adverse Reaction

Placebo

n = 176

BETAFERON

n = 292

Peripheral oedema

Asthaenia

Chills

Sweating

Malaise

Significantly associated with BETAFERON treatment for patients with first event suggestive of MS,

<

0.05

Injection site reaction (various kinds) comprises all adverse events occurring at the injection site, i.e. the

following terms: injection site haemorrhage, injection site hypersensitivity, injection site inflammation,

injection site mass, injection site necrosis, injection site pain, injection site reaction, injection site oedema, and

injection site atrophy and flu like symptom complex denotes flu syndrome and/or a combination of at least

two AEs from fever, chills, myalgia, malaise, sweating.

During the third year of the BENEFIT study, no change of the known risk profile of BETAFERON was observed

Post-marketing Information

Anecdotal evidence from post-marketing experience suggests that systemic flu-like symptoms can be

substantially suppressed by the concomitant administration of paracetamol or ibuprofen.

The following adverse reactions have been reported at the approximate frequencies (not necessarily

implicating a causal relationship) indicated below:

Very common

≥ 1/10

Common

≥ 1/100

< 1/10

Uncommon

≥ 1/1 000

< 1/100

Rare

≥ 1/10 000

< 1/1 000

Very rare

< 1/10 000

Adverse Events and Laboratory Abnormalities

Body System

Reporting Rate

Adverse Reaction

Blood and Lymphatic System

Disorders

Uncommon

Anaemia,

Thrombocytopaenia,

Leukopaenia

Rare

Lymphadenopathy

Thrombotic microangiopathy

Immune System Disorders

Rare

Anaphylactic reactions

Endocrine Disorders

Rare

Hyperthyroidism,

Hypothyroidism, Thyroid

dysfunction

Metabolism and Nutrition

Disorders

Rare

Triglyceride increase

Anorexia,

Weight increase

Weight decrease

Psychiatric Disorders

Uncommon

Depression

1902 BETAFERON DS

Page 14 of 23

Rare

Confusion,

Anxiety,

Emotional lability,

Suicide attempt

Nervous System Disorders

Rare

Convulsion,

Dizziness

Cardiac Disorders

Rare

Cardiomyopathy,

Tachycardia,

Palpitation

Vascular Disorders

Uncommon

Hypertension

Very rare

Vasodilatation

Respiratory Disorders

Rare

Bronchospasm,

Dyspnoea

Gastrointestinal Disorders

Uncommon

Nausea,

Vomiting,

Rare

Pancreatitis

Diarrhoea

Hepatobiliary Disorders

Uncommon

ALT increase,

AST increase

Rare

Hepatic injury (including

Hepatitis)

Gamma GT increase,

Blood Bilirubin increase

Skin and Subcutaneous Tissue

Disorders

Uncommon

Alopaecia,

Urticaria,

Pruritus,

Rash

Rare

Skin discolouration,

Musculoskeletal, connective

tissue and bone disorders

Uncommon

Myalgia,

Hypertonia

Rare

Arthralgia

Renal disorders

Uncommon

Nephrotic syndrome

Reproductive system disorders

Rare

Menstrual disorder

Very rare

Menorrhagia

General Disorders and

Administration Site Conditions

Very common

Flu-like symptoms

, Chills

Fever

Injection site reaction

Injection site inflammation

Injection site pain

Common

Injection site necrosis

Rare

Chest pain,

Malaise,

Sweating

frequencies based on clinical trials

1902 BETAFERON DS

Page 15 of 23

Capillary leak syndrome in pre-existing monoclonal gammopathy, hepatic failure, drug-induced lupus

erythematosus and pulmonary arterial hypertension (PAH) has been reported in post-marketing

surveillance. The frequency cannot be estimated from the available data and is therefore unknown.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Serum samples in controlled

clinical trials were collected every 3 months (in the study of patients with a single clinical event

suggestive of MS every 6 months) for monitoring of development of antibodies to BETAFERON. In the

different controlled clinical trials in relapsing remitting multiple sclerosis and secondary progressive

multiple sclerosis, between 23% and 41% of the patients developed serum interferon beta-1b

neutralising activity confirmed by at least two consecutive positive titres; of these patients, between

43% to 55% converted to a stable antibody negative status (based on two consecutive negative titers)

during the subsequent observational period of the respective study.

In the study of patients with a single clinical event suggestive of multiple sclerosis, neutralising activity

measured every 6 months was observed at least once in 32% (89) of the patients treated immediately

with BETAFERON; of these, 60% (53) returned to negative status based on the last available

assessment within the five year period. Within the study period of five years the development of

neutralising activity was not associated with a reduction in clinical efficacy with regard to time to

clinically definite multiple sclerosis (CDMS) and time to confirmed EDSS progression and relapse rate.

consistent

attenuating

effects

clinical

outcomes,

including

findings,

have

been

demonstrated related to the presence of neutralising antibodies, across studies, endpoints, different

statistical approaches and varying definitions of neutralising antibody positive status. Adverse events

have not been associated with the development of neutralising activity.

The decision to continue or discontinue treatment should be based on all aspects of the patient’s

disease status rather than on neutralising activity status alone.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are

asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

Overdose

Interferon beta-1b has been given without serious adverse events compromising vital functions to

adult cancer patients at individual doses as high as 5.5 mg (176 million IU) i.v. three times a week.

There have been no reported cases of accidental overdose.

For advice on the management of overdose please contact the National Poisons Centre on 0800

POISON (0800 764766).

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group: Cytokines, Interferons, ATC Code: L03AB08

Interferon

beta-1b

purified,

sterile

lyophilised

protein

that

amino

acids

approximate molecular weight of 18,500 Daltons.

1902 BETAFERON DS

Page 16 of 23

Interferon beta-1b differs structurally from natural human interferon beta by the presence of serine

instead of cysteine in position 17, lack of methionine in position 1 and absence of carbohydrate

moieties.

Interferons belong to the family of cytokines, which are naturally occurring proteins. Interferons have

molecular weights ranging from 15,000 to 21,000 Daltons. Three major classes of interferons have

been identified: alpha, beta, and gamma. Interferon alpha, interferon beta, and interferon gamma

have overlapping yet distinct biological activities. The activities of interferon beta-1b are generally

species restricted, and therefore the most pertinent pharmacological information on interferon beta-

1b is derived from studies of human cells in culture or in human in vivo studies.

BETAFERON

been

shown

possess

both

antiviral

immunoregulatory

activities.

mechanisms by which interferon beta-1b exerts its actions in multiple sclerosis (MS) are not clearly

understood. However, it is known that the biological response-modifying properties of interferon

beta-1b are mediated through its interactions with specific cell receptors found on the surface of

human cells. The binding of interferon beta-1b to these receptors induces the expression of a number

of gene products that are believed to be the mediators of the biological actions of interferon beta-1b.

A number of these products have been measured in the serum and cellular fractions of blood collected

from patients treated with interferon beta-1b.

Interferon

beta-1b

both

decreases

binding

affinity

enhances

internalisation

degradation of the interferon-

receptor. Interferon beta-1b also enhances the suppressor activity of

peripheral blood mononuclear cells.

separate

investigations

were

performed

regarding

influence

BETAFERON

cardiovascular system, respiratory system and the function of endocrine organs.

Clinical efficacy and safety

Single Clinical Event Suggestive of Multiple Sclerosis

One multi-centred, randomised, placebo-controlled, double-blind, clinical efficacy and safety study

(BENEFIT) was performed in patients with a single clinical demyelinating event suggestive of MS and

at least two clinically silent magnetic resonance imaging (MRI) lesions characteristic of MS. The study

enrolled patients within 60 days after the onset of a single clinical event suggestive of MS, based on

the appearance of a new neurological abnormality which had to be present for at least 24 hours. The

T2-weighted brain MRI scan had to show at least two clinically silent lesions with a size of at least 3

mm, at least one of which had to be ovoid or periventricular or infratentorial. Patients were aged 18

to 45 years with an expanded disability status scale (EDSS) of ≤ 5.0. Patients with monofocal or

multifocal onset of the disease were included (i.e. patients with clinical evidence of a single or at

least two lesions, respectively, of the central nervous system). Patients with any disease other than

multiple sclerosis that could better explain the signs and symptoms had to be excluded.

This study consisted of two phases, a placebo-controlled phase followed by a pre-planned follow-up

phase. The placebo-controlled phase lasted for 2 years or until the patient developed clinically

definite multiple sclerosis (CDMS), whichever came first. After the placebo-controlled phase,

patients entered a pre-planned follow-up phase with BETAFERON to evaluate the effects of

immediate versus delayed start of BETAFERON-treatment, comparing patients initially randomised

to BETAFERON (“immediate treatment group”) or to placebo (“delayed treatment group”). Patients

and investigators remained blinded to the initial treatment allocation.

1902 BETAFERON DS

Page 17 of 23

The two primary efficacy variables were time to onset of clinically definite MS (CDMS), and time to

onset of MS according to McDonald diagnostic criteria. Clinically definite MS was reached if the

patient experienced a relapse of the disease, or a sustained progression of ≥ 1.5 points on the EDSS

scale as compared to the lowest EDSS obtained during the screening on day 1 reaching a total EDSS

score of ≥ 2.5. Multiple sclerosis according to the McDonald criteria was reached if, in addition to the

single clinical demyelinating event, both dissemination in space and dissemination in time had been

established.

Patients selected for the study were randomised to treatment with either 0.25 mg (8 million IU)

BETAFERON (n = 292) or placebo (n = 176) self-administered subcutaneously every second day for a

treatment duration of up to 2 years.

In the placebo-controlled phase, BETAFERON delayed the progression from the first clinical event to

clinically definite MS in a statistically significant and clinically meaningful manner compared with

placebo, corresponding to a risk reduction of 47% (hazard ratio = 0.53; 95% confidence interval

[0.39, 0.73], p <0.0001). A post-hoc analysis adjusting for standard baseline covariates revealed a risk

reduction by 50%. Within two years, CDMS occurred in 45% of the placebo group compared to 28%

of the BETAFERON group (Kaplan-Meier estimates). BETAFERON prolonged the time to CDMS by 363

days, from 255 days in the placebo group to 618 days in the BETAFERON group (based on 25

percentiles).

BETAFERON also statistically significantly delayed the progression to MS according to the McDonald

criteria compared with placebo, corresponding to a risk reduction of 43% (hazard ratio = 0.57; 95%

confidence interval [0.46, 0.71], p <0.00001). In the first six months, a diagnosis of MS according to

the McDonald criteria was made in 51% of placebo and 28% of BETAFERON patients, and after two

years, the respective incidences were 85% and 69% (Kaplan-Meier estimates).

After the placebo-controlled phase, patients entered a pre-planned follow-up phase with

BETAFERON to evaluate the effects of immediate versus delayed start of BETAFERON-treatment,

comparing patients initially randomised to BETAFERON (“immediate treatment group”) or to placebo

(“delayed treatment group”). Patients and investigators remained blinded to the initial treatment

allocation. The two pre-planned analyses at three and five years include integrated data of the

placebo-controlled and the follow-up phase for the first three years and the entire five year

observation period, respectively.

Immediate BETAFERON-treatment delayed the progression from the first clinical event to CDMS in a

statistically significant and clinically meaningful manner, corresponding to a risk reduction of 41%

(Hazard Ratio = 0.59, 95% CI (0.42, 0.83), p=0.0011) over three years and 37% over five years. At

three years, CDMS had occurred in 51% of the delayed treatment group compared to 37% of the

immediate treatment group (Kaplan-Meier estimates – see Figure 1). At five years, 57% of the

delayed treatment group and 46% of the immediate treatment group were diagnosed with CDMS.

This effect was observed even though the majority of patients from the original placebo-group were

treated with BETAFERON at least from the second year onwards.

Immediate BETAFERON-treatment reduced risk for confirmed disability progression by 40% (Hazard

Ratio = 0.60, 95% CI (0.39-0.92), p=0.022) as compared to delayed start of treatment. Over three

years EDSS progression occurred in 24% of the patients in the delayed treatment group compared to

16% of the patients in the immediate treatment group (see Figure 2).

At three years immediate BETAFERON-treatment as compared to a delayed start of treatment

reduced the risk for confirmed disability progression by 40% (statistically significant). Over five years

1902 BETAFERON DS

Page 18 of 23

the risk reduction (24%) was no longer statistically significant. Disability progression had occurred in

29% of the delayed treatment group compared to 25% of the early treatment group.

1902 BETAFERON DS

Page 19 of 23

Two MRI-derived parameters, the cumulative number of newly active lesions and the change in T2

lesion volume, were analysed as secondary efficacy variables. The cumulative number of newly

active lesions up to end of study was statistically significantly lower in the BETAFERON group,

irrespective of whether annualised (median number of newly active lesions was 1.34 for BETAFERON

and 3.16 for placebo), or non-annualised (median number of newly active lesions was 2.0 for

BETAFERON and 4.0 for placebo) values were considered (p <0.0001 for both analyses). The non-

annualised T2 lesion volume reduction up to the last scan was statistically significantly higher in the

BETAFERON group (median change -206.0 mm

for BETAFERON vs -93.00 mm

for placebo; p =

0.0498, but not for the annualised values (median change -119.70 mm

for BETAFERON vs -57.54

for placebo; p = 0.1906).

In a questionnaire assessing health-related quality of life as reported by the patient (Functional

Assessment of MS), scores remained high and stable throughout the five years, significant

differences between the two treatment groups could not be demonstrated.

Relapsing-remitting multiple sclerosis

BETAFERON was shown to reduce the frequency and severity of clinical relapses, to reduce the

number of MS related hospitalisations and steroid usage to prolong the exacerbation-free time in

patients with both relapsing-remitting multiple sclerosis (EDSS 0-5.5) and secondary progressive

multiple sclerosis (EDSS 3.0 – 6.5).

Furthermore, BETAFERON has a significant beneficial effect on disease burden and activity as

measured by magnetic resonance imaging (MRI); an increase in MRI disease burden has been

demonstrated to correlate with an increase in disability as measured by expanded disability status

scale (EDSS).

Secondary progressive multiple sclerosis

Patients with secondary progressive disease receiving BETAFERON showed a delay of up to 12 months

in time to progression of disability including time to severely disabling stages, i.e. patients becoming

wheelchair bound. This delay in disability occurred in patients with or without relapses and at all levels

of disability investigated (EDSS 3-6.5).

Both relapsing-remitting and secondary progressive multiple sclerosis patients receiving BETAFERON

showed a reduction in frequency (30%) and severity of clinical relapses, as well as a prolongation of

the relapse-free interval. The number of hospitalisations and steroid usage due to disease was

reduced.

Furthermore, in both relapsing-remitting and secondary progressive multiple sclerosis BETAFERON

demonstrated a significant beneficial effect on disease burden as measured by T2-weighted MRI scans

and on newly active lesions as measured by six weekly MRIs in relapsing-remitting MS and by monthly

contrast medium (Gd-DTPA) enhanced T1 weighted MRIs (months 1-6 and 19-24) in secondary-

progressive MS. An increase in MRI disease burden has been demonstrated to correlate with an

increase in disability as measured by expanded disability status scale.

Pharmacokinetic properties

BETAFERON serum levels were followed in patients and volunteers by means of a non-specific

bioassay. Following subcutaneous administration of the recommended dose of 8 million IU (0.25 mg)

or less of interferon beta-1b, serum concentrations of interferon beta-1b are low or not detectable.

1902 BETAFERON DS

Page 20 of 23

Pharmacokinetic information in patients with MS receiving the recommended dose of BETAFERON is

therefore not available.

Absorption

Following subcutaneous injection of 0.5 mg of interferon beta-1b to healthy volunteers, maximum

serum levels of about 40 IU/mL were found 1-8 hours after dosing. In this study, the absolute

bioavailability of subcutaneously administered BETAFERON was estimated at approximately 50%.

From various studies with intravenous administration of interferon beta-1b, mean clearance and

disposition half-life from serum were estimated to be at most 30 mL/min/kg and 5 hours,

respectively.

After intravenous administration of interferon beta-1b in a dosage range of 0.2 million IU (0.0006

mg) to 64 million IU (2.0 mg), similar pharmacokinetic profiles were obtained from healthy

volunteers and from patients with diseases other than MS. In patients receiving single intravenous

doses of up to 64 million IU (2.0 mg), increases in serum concentrations were dose proportional.

Mean serum clearance values of up to 28.9 mL/min.kg

were observed.

Every other day BETAFERON injections do not lead to serum level increases and pharmacokinetics do

not seem to change during therapy.

Elimination

Mean terminal elimination half-life and steady-state volume of distribution were estimated to be at

most 4.3 hours and 2.88 L/kg. Three-times-a-week intravenous dosing for 2 weeks resulted in no

accumulation of interferon beta-1b in the serum of patients. Pharmacokinetic parameters after

single and multiple intravenous doses of interferon beta-1b were comparable.

Following every-other-day subcutaneous administration of 0.25 mg (8 million IU) of interferon beta-

1b in healthy volunteers, biologic response marker levels (neopterin, ß2-microglobulin and the

immunosuppressive cytokine, IL-10) increased significantly above baseline levels within 6 to 12

hours after the first BETAFERON dose. Biologic response marker levels peaked between 40 and 124

hours, and remained elevated above baseline throughout the 7 day (168 hour) study period. The

relationship between serum interferon beta-1b levels or the levels of induced biologic response

markers to the mechanism by which BETAFERON exerts its effects in MS is unknown.

Preclinical safety data

No acute toxicity studies have been carried out. As rodents do not react to human interferon beta,

risk assessment was based on repeated dose studies carried out with rhesus monkeys.

Transitory hyperthermia was observed, as well as a significant transient rise in lymphocytes and a

significant transient decrease in thrombocytes and segmented neutrophils. No long-term studies

have been conducted.

Although acute toxicity studies have not been carried out, an experimental primate study using daily

intravenous and subcutaneous administration did not reveal any untoward acute effects of

treatment. This study showed a potential for interferon beta-1b treatment to elicit transient

pyrogenic and haematological effects, including neutropaenia and thrombocytopaenia. Pronounced

thrombocytopaenia or anaemia was seen in some pregnant experimental primates after daily

treatment with high doses of interferon beta-1b (8 million IU/kg and above). The long term toxicity

of interferon beta-1b has not been investigated in any experimental species.

1902 BETAFERON DS

Page 21 of 23

Based on experiments using other interferons, a potential risk of impaired male and female fertility

cannot be ruled out.

Specific testing for contact sensitivity was not carried out, but delayed type hypersensitivity

reactions specific for interferon beta-1b were not seen in experimental primates after daily

intravenous or subcutaneous administration. However, serum anti-interferon beta-1b antibodies

were measurable in these animals.

In one single genotoxicity study (Ames test), no mutagenic effect has been observed. An in vitro cell

transformation test gave no indication of tumourigenic potential.

PHARMACEUTICAL PARTICULARS

List of excipients

Lyophilisate: human albumin, mannitol

Solvent: sodium chloride, water for injection

Incompatibilities

Not applicable

Shelf life

As packaged for sale, 24 months starting from the date of sterile filtration of the formulated

bulk solution

After reconstitution according to the directions: up to 3 hours at 2 – 8 °C.

Special precautions for storage

Before reconstitution, store at or below 25°C.

After reconstitution, store at 2 – 8°C for up to 3 hours.

Nature and contents of container and special equipment for use, administration or

implantation

BETAFERON is presented as a 3 mL clear glass vial containing powder for solution for injection with

13 mm black chlorinated butyl rubber stopper and aluminium overseal.

Each BETAFERON vial is provided with a separate 2.25 mL pre-filled syringe of diluent, containing 1.2

mL of sterile sodium chloride solution (0.54% w/v).

Each vial contains 0.3 mg (9.6 million IU) of interferon beta-1b at a calculated overfill of 20%

allowing extraction of the nominal content of 8 million IU (0.25 mg) in 1 mL after reconstitution with

1.2 mL of diluent.

The multipack comprises 15 single use packs, each containing 1 BETAFERON vial with powder, 1 pre-

filled syringe with diluent, 1 vial adapter with needle, and 2 alcohol wipes.

Special precautions for disposal and other handling

Reconstitution

To reconstitute lyophilised interferon beta-1b for injection, connect the vial adapter with attached

needle on the vial. Connect the pre-filled syringe with solvent to the vial adapter and inject the 1.2

1902 BETAFERON DS

Page 22 of 23

mL of the diluent (sodium chloride, 0.54% w/v solution) it contains, into the BETAFERON vial.

Dissolve the powder completely without shaking.

Inspect the reconstituted product visually before use. The reconstituted product is colourless to light

yellow and slightly opalescent to opalescent. Discard the product if it contains particulate matter or

is discoloured. The reconstituted solution contains 8 million IU (0.25 mg) of interferon beta-1b per

After reconstitution, draw 1.0 mL from the vial into the syringe for administration of 0.25 mg

BETAFERON. Remove the vial with the vial adapter from the pre-filled syringe by twisting the vial and

then pulling it down, away from the syringe before injection. For dose titration at the start of

treatment, draw the respective volume as given in Table A. Proceed to inject appropriate volume of

injection. Discard any unused solution for injection.

To reduce microbiological hazard, the reconstituted solution should be used as soon as practicable

after reconstitution. If storage is necessary, hold at 2

C to 8

C for not more than 3 hours.

In the absence of compatibility studies, this medicinal product should not be mixed with other

medicinal products.

Detailed instructions for the self-injection procedure can be found in the Consumer Medicine

Information. For auto-injection, please refer to the manufacturer’s instructions for use of the auto-

injector.

Inspection Prior To Use

Inspect the reconstituted product visually before use. Discard the product before use if it contains

particulate matter or is discoloured. The reconstituted solution contains 0.25 mg (8 million IU) of

interferon beta-1b per mL.

To reduce microbiological hazard, the reconstituted solution should be used as soon as practicable

after reconstitution. If storage is necessary, hold at

2°C to 8°C for not more than 3 hours.

MEDICINE SCHEDULE

Prescription Medicine

SPONSOR

Bayer New Zealand Limited

3 Argus Place

Hillcrest

North Shore

Auckland 0627

Free Phone 0800 233 988

www.bayer.co.nz

DATE OF FIRST APPROVAL

13 December 2016

1902 BETAFERON DS

Page 23 of 23

DATE OF REVISION OF THE TEXT

20 February 2019

SUMMARY TABLE OF CHANGES

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